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Wolfgang Bernhard Liedtke

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Liedtke in 2023

Wolfgang Bernhard Liedtke is a German-American neurologist and corporate executive at Regeneron Pharmaceuticals in Tarrytown, New York. Within Regeneron's Global Development (Genetic Medicines), he serves as the Chair of Neurology, Psychiatry, Pain Medicine, and Sensory Systems on the Scientific Council.[1][2][3]

Liedtke also holds positions as an adjunct professor of Neurology at Duke University in Durham, North Carolina, and as an adjunct professor at New York University (NYU) College of Dentistry in New York City, where he is affiliated with the Department of Molecular Pathobiology and Dental Pain Research. He is also a Member of the NYU Pain Research Center.[4][5][6]

Early life and education

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Liedtke was born in Dortmund, Germany. He was educated in Germany in higher education and studied medicine at Ruhr University Bochum as a scholar of the German Academic Scholarship Foundation (Studienstiftung des Deutschen Volkes).[7][8] After MD (University of Cologne), PhD (virology, Ruhr University Bochum, graduating magna cum laude)[9][3], residencies in neurology (University Hospitals of Tuebingen Essen, Germany), psychiatry (University Hospital and State Psychiatric Hospital, Essen) and fellowship in neuropathology (Albert Einstein College of Medicine of Yeshiva University in The Bronx, New York City[8][3], supported by the Alexander von Humboldt Foundation, Bonn, Germany, recipient of a Feodor Lynen Fellowship.[8][10] Liedtke joined the metabolism-genetics laboratory of Howard Hughes Investigator Jeffrey M. Friedman at the Rockefeller University in New York City, NY, as a Senior Research Associate and then as a Research Assistant Professor (1997-2004).[10][8]

Career

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Liedtke was selected as the Ebert Clinical Fellow-Klingenstein Fellow of the Klingenstein Fund in 2004.[11][12] From 2004 to 2021, Liedtke held the position of scientist-physician academic professor at Duke University, where he focused on discoveries related to TRPV4.[13][3][14][15] He was awarded tenure in 2014 and became a full professor in 2016.

In 2013, he was selected as a Harrington Discovery Institute Scholar-Innovator of the Harrington Discovery Institute in Cleveland, Ohio, and in 2019 he presented the Blaustein Pain Lecture at Johns Hopkins Hospital in Baltimore.[16][17]

In 2020, Liedtke was selected Fellow of the Innovation-to-Impact Entrepreneurship Program of Yale University.[9]

In April 2021, he joined Regeneron, where he is a member of the Scientific Council in Global Development - Genetic Medicines.[18]

In November 2023, Liedtke was elected to the American Clinical and Climatological Association in Little Rock, Arkansas, one of 250 member physicians.[9]

As a physician in the Duke Health system, he provided clinical care in his neurology and anesthesiology clinics.[19] Liedtke treated patients suffering from refractory pain, mostly nerve pain of the trigeminal and glossopharyngeal nerve, but also oro-facial-head pain and generalized nerve pain.[20] At Duke University, he was a Distinguished Nominee for the Leonard Tow Humanism in Medicine Award in 2017 and 2018 (Gold Foundation, Englewood Cliffs, NJ).[9]

Since August 2021, he has been a member of the Medical Advisory Board of the Facial Pain Association (FPA), serving as their Lead Neurologist, also since 2024 as their Medical Lead of the FPA's Patient Registry.[21]

By mid-2024, he was selected as Senior Advisor to the Davos Alzheimer's Collaborative.[22][23]

Scientific work

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Liedtke first described the TRPV4 ion channel, originally named vanilloid receptor-related osmotically activated channel (VR-OAC), the first vertebrate osmotically activated ion channel.[24]

His original report on TRPV4, published in the journal Cell, has been widely cited in the scientific community, with 1594 references as of October 2024 (1154 references in SCOPUS).[25]

Liedtke described TRPV4 as the first vertebrate osmoreceptor ion channel with possible wide organismal physiologic function including sensory function and pain. He then characterized TRPV4 in live animals, mice and worms. In worms, he identified TRPV4 as a functional orthologue of the ancestral TRPV channel, OSM-9, for mechanical and osmotic sensing.[26][27]

TRPV4 was the first TRPV channel discovered outside of David Julius' research group. Liedtke characterized the role of TRPV4 in trigeminal pain as well as its role as a UVB receptor in epithelial skin cells and in itch, including in debilitating itch associated with chronic liver disease.[14][28] Rooted in his TRPV4-pain related discoveries, he co-founded the pain research group at Duke University.[1]

A symposium titled "20 years of TRPV4 – Exploring Science, Discovery, and Future Directions" was organized by InsideScientific, with official support from the American Physiological Society.[29][30] Liedtke served as the Program Chair for this international conference, which covered scientific topics of mammalian physiology and human health, related to Liedtke's discovery of TRPV4 and its therapeutic impact.[31][32] Liedtke had 104 peer-reviewed scientific publications linked to TRPV4 in SCOPUS as of June 2023. He is the most active contributor to the field, with approximately 5% of all peer-reviewed publications related to TRPV4. His TRPV4-related work has been referenced 12597 times, accounting for 14.2% of the entire TRPV4 field's citations.

In addition to his work on the identification of TRPV4, Liedtke published discoveries on gene regulation of the Kcc2/KCC2 gene, which maintains low intraneuronal chloride levels in the central nervous system (CNS), thus enabling normal CNS function in vertebrates.[33][34] This mechanism is derailed in chronic pain, epilepsy, traumatic injury of the brain and spinal cord, likely neurodegeneration and psychoses, and possibly Long-Neuro-COVID.[35][36]

Liedtke also contributed to the understanding of cartilage mechanobiology, working together with Farshid Guilak.[37][38]

Entrepreneurial activities

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Liedtke holds six granted U.S. patents related to TRPV4 and is a contributor on eight additional pending patents based on TRPV4-related discoveries in his laboratory.

The following granted U.S. patents list Liedtke as lead inventor: 9290489,[39] 9701675,[40] 10329265,[41] 11014896,[42] 11229628,[43] 11564911.[44] Based on these patents, Liedtke co-founded TRPblue Inc. (Durham NC). TRPblue is a biotech start-up company that received support from the Medblue Incubator (Durham, NC), NC Biotech (Research Triangle Park, NC), and the US National Institutes of Health.[45][46]

References

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  1. ^ a b "Loop | Wolfgang B Liedtke". loop.frontiersin.org. Retrieved 2023-11-17.
  2. ^ FAAD, Marie Benz MD (2021-04-05). "Mechanism of Horrible Itching of Liver Disease Identified in Superficial Skin Cells". Retrieved 2023-11-17.
  3. ^ a b c d "Wolfgang Bernhard Liedtke". scholars.duke.edu. Retrieved 2023-11-17.
  4. ^ "Unveiling the Mystery of Migraines". Duke Department of Neurology. 2023-05-24. Retrieved 2023-11-17.
  5. ^ "PART-TIME FACULTY DIRECTORY". Retrieved 2023-11-17.
  6. ^ "Dr. Wolfgang B Liedtke, Neurology, Durham NC". TopNPI. Retrieved 2023-11-17.
  7. ^ "Studienstiftung des deutschen Volkes" (PDF). studienstiftung.de. 2013. Retrieved 2023-11-17.
  8. ^ a b c d TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades., CRC Press/Taylor & Francis, 2007, retrieved 2023-11-17
  9. ^ a b c d "Loop | Wolfgang B Liedtke". loop.frontiersin.org. Retrieved 2023-11-17.
  10. ^ a b "Scientists Report Cancer Fighting Drug As Possible Treatment For Multiple Sclerosis". ScienceDaily. Retrieved 2023-11-17.
  11. ^ "Robert H. Ebert Clinical Scholarship". Klingenstein Philanthropies. Retrieved 2023-11-17.
  12. ^ "Wolfgang B. Liedtke, Ph.D." Klingenstein Philanthropies. Retrieved 2023-11-17.
  13. ^ "Wolfgang Bernhard Liedtke | Duke Neurobiology". www.neuro.duke.edu. Retrieved 2023-11-17.
  14. ^ a b Moore, Carlene; Cevikbas, Ferda; Pasolli, H. Amalia; Chen, Yong; Kong, Wei; Kempkes, Cordula; Parekh, Puja; Lee, Suk Hee; Kontchou, Nelly-Ange; Yeh, Iwei; Jokerst, Nan Marie; Fuchs, Elaine; Steinhoff, Martin; Liedtke, Wolfgang B. (2013-08-20). "UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling". Proceedings of the National Academy of Sciences. 110 (34): E3225-34. Bibcode:2013PNAS..110E3225M. doi:10.1073/pnas.1312933110. ISSN 0027-8424. PMC 3752269. PMID 23929777.
  15. ^ Chen, Yong; Wang, Zi-Long; Yeo, Michele; Zhang, Qiao-Juan; López-Romero, Ana E.; Ding, Hui-Ping; Zhang, Xin; Zeng, Qian; Morales-Lázaro, Sara L.; Moore, Carlene; Jin, Ying-Ai; Yang, Huang-He; Morstein, Johannes; Bortsov, Andrey; Krawczyk, Marcin (2021-07-01). "Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine". Gastroenterology. 161 (1): 301–317.e16. doi:10.1053/j.gastro.2021.03.049. ISSN 0016-5085. PMC 9093619. PMID 33819485.
  16. ^ "Wolfgang Liedtke, MD, PhD | Scholars | Harrington Discovery Institute at University Hospitals". www.harringtondiscovery.org. Retrieved 2023-11-17.
  17. ^ "The Blaustein Pain Research and Education Endowment". www.hopkinsmedicine.org. Retrieved 2023-11-17.
  18. ^ "New life for a cancer drug that reprograms pain pathways to treat chronic pain". oncologynews.com. November 5, 2021. Retrieved 2023-11-17.
  19. ^ "Wolfgang Bernhard Liedtke | Duke University School of Medicine". medschool.duke.edu. Retrieved 2023-11-17.
  20. ^ "Dr. Wolfgang B. Liedtke MD". health.usnews.com. Retrieved 2023-11-17.
  21. ^ "About Facial Pain Association: Our Mission and Team". Facial Pain Association. 2021-04-08. Retrieved 2023-11-17.
  22. ^ "About". Davos Alzheimer’s Collaborative. Retrieved 2024-06-04.
  23. ^ "Partnership Launched to Fight Alzheimer's Worldwide". World Economic Forum. 25 January 2021.
  24. ^ Wolfgang, Liedtke; Choe, Yong; Martí-Renom, Marc A.; Bell, Andrea M.; Denis, Charlotte S.; Šali, Andrej; Hudspeth, A.J.; Friedman, Jeffrey M.; Heller, Stefan. "Vanilloid Receptor–Related Osmotically Activated Channel (VR-OAC), a Candidate Vertebrate Osmoreceptor".
  25. ^ "Академия Google". scholar.google.com. Retrieved 2023-11-17.
  26. ^ Liedtke, Wolfgang; Friedman, Jeffrey M. (2003-11-11). "Abnormal osmotic regulation in trpv4 -/- mice". Proceedings of the National Academy of Sciences. 100 (23): 13698–13703. Bibcode:2003PNAS..10013698L. doi:10.1073/pnas.1735416100. ISSN 0027-8424. PMC 263876. PMID 14581612.
  27. ^ Liedtke, Wolfgang; Tobin, David M.; Bargmann, Cornelia I.; Friedman, Jeffrey M. (2003-11-25). "Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans". Proceedings of the National Academy of Sciences. 100 (suppl_2): 14531–14536. Bibcode:2003PNAS..10014531L. doi:10.1073/pnas.2235619100. ISSN 0027-8424. PMC 304114. PMID 14581619.
  28. ^ Chen, Yong; Wang, Zi-Long; Yeo, Michele; Zhang, Qiao-Juan; López-Romero, Ana E.; Ding, Hui-Ping; Zhang, Xin; Zeng, Qian; Morales-Lázaro, Sara L.; Moore, Carlene; Jin, Ying-Ai; Yang, Huang-He; Morstein, Johannes; Bortsov, Andrey; Krawczyk, Marcin (2021). "Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine". Gastroenterology. 161 (1): 301–317.e16. doi:10.1053/j.gastro.2021.03.049. ISSN 0016-5085. PMC 9093619. PMID 33819485.
  29. ^ hayleighisc. "20 Years of TRPV4: Exploring Science, Discovery, and Future Directions". InsideScientific. Retrieved 2023-11-17.
  30. ^ "20 Years of TRPV4: Exploring Science, Discovery, and Future Directions". BigMarker.com. Retrieved 2023-11-17.
  31. ^ Liedtke, Wolfgang; Choe, Yong; Martí-Renom, Marc A.; Bell, Andrea M.; Denis, Charlotte S.; AndrejŠali; Hudspeth, A.J.; Friedman, Jeffrey M.; Heller, Stefan (2000). "Vanilloid Receptor–Related Osmotically Activated Channel (VR-OAC), a Candidate Vertebrate Osmoreceptor". Cell. 103 (3): 525–535. doi:10.1016/s0092-8674(00)00143-4. ISSN 0092-8674. PMC 2211528. PMID 11081638.
  32. ^ Moore, Carlene; Gupta, Rupali; Jordt, Sven-Eric; Chen, Yong; Liedtke, Wolfgang B. (2018-02-01). "Regulation of Pain and Itch by TRP Channels". Neuroscience Bulletin. 34 (1): 120–142. doi:10.1007/s12264-017-0200-8. ISSN 1995-8218. PMC 5799130. PMID 29282613.
  33. ^ Yeo, Michele; Berglund, Ken; Augustine, George; Liedtke, Wolfgang (2009-11-18). "Novel Repression of Kcc2 Transcription by REST–RE-1 Controls Developmental Switch in Neuronal Chloride". Journal of Neuroscience. 29 (46): 14652–14662. doi:10.1523/JNEUROSCI.2934-09.2009. ISSN 0270-6474. PMC 2833346. PMID 19923298.
  34. ^ Liedtke, Wolfgang (2022). "Long March Toward Safe and Effective Analgesia by Enhancing Gene Expression of Kcc2: First Steps Taken". Frontiers in Molecular Neuroscience. 15. doi:10.3389/fnmol.2022.865600. ISSN 1662-5099. PMC 9137411. PMID 35645734.
  35. ^ Kahle, Kristopher T.; Khanna, Arjun; Clapham, David E.; Woolf, Clifford J. (2014-05-01). "Therapeutic Restoration of Spinal Inhibition via Druggable Enhancement of Potassium-Chloride Cotransporter KCC2–Mediated Chloride Extrusion in Peripheral Neuropathic Pain". JAMA Neurology. 71 (5): 640–645. doi:10.1001/jamaneurol.2014.21. ISSN 2168-6149. PMC 4465580. PMID 24615367.
  36. ^ Price, Theodore J.; Cervero, Fernando; Koninck, Yves de (2005-06-01). "Role of Cation-Chloride-Cotransporters (CCC) in Pain and Hyperalgesia". Current Topics in Medicinal Chemistry. 5 (6): 547–555. doi:10.2174/1568026054367629. PMC 1472095. PMID 16022677.
  37. ^ Lee, Whasil; Leddy, Holly A.; Chen, Yong; Lee, Suk Hee; Zelenski, Nicole A.; McNulty, Amy L.; Wu, Jason; Beicker, Kellie N.; Coles, Jeffrey; Zauscher, Stefan; Grandl, Jörg; Sachs, Frederick; Guilak, Farshid; Liedtke, Wolfgang B. (2014-11-25). "Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage". Proceedings of the National Academy of Sciences. 111 (47): E5114-22. Bibcode:2014PNAS..111E5114L. doi:10.1073/pnas.1414298111. ISSN 0027-8424. PMC 4250098. PMID 25385580.
  38. ^ Lee, W.; Guilak, F.; Liedtke, W. (2017). "Role of Piezo Channels in Joint Health and Injury". Current Topics in Membranes. 79: 263–273. doi:10.1016/bs.ctm.2016.10.003. ISBN 9780128093894. ISSN 1063-5823. PMC 5681866. PMID 28728820.
  39. ^ "Activation of TRPV4 ion channel by physical stimuli and critical role for TRPV4 in organ-specific inflammation and itch". app.dimensions.ai. Retrieved 2023-11-17.
  40. ^ US9701675B2, Liedtke, Wolfgang; Steinhoff, Martin & Guilak, Farshid, "Activation of TRPV4 ion channel by physical stimuli and critical role for TRPV4 in organ-specific inflammation and itch", issued 2017-07-11 
  41. ^ "TRPA1 and TRPV4 inhibitors and methods of using the same for organ-specific inflammation and itch". app.dimensions.ai. Retrieved 2023-11-17.
  42. ^ "US Patent for TRPA1 and TRPV4 inhibitors and methods of using the same for organ-specific inflammation and itch Patent (Patent # 11,014,896 issued May 25, 2021) - Justia Patents Search". patents.justia.com. Retrieved 2023-11-17.
  43. ^ US11229628B2, Liedtke, Wolfgang, "TRPA1 and TRPV4 inhibitors and methods of using the same for organ-specific inflammation and itch", issued 2022-01-25 
  44. ^ EP2869897A2, Liedtke, Wolfgang; Steinhoff, Martin & Guilak, Farshid, "Activation of trpv4 ion channel by physical stimuli and critical role for trpv4 in organ-specific inflammation and itch", issued 2015-05-13 
  45. ^ "Companies". medblueincubator.com. Retrieved 2023-11-17.
  46. ^ "TRPblue Inc. | North Carolina Biotech Center". directory.ncbiotech.org. Retrieved 2023-11-17.
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